The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis

Int Immunol. 2004 Mar;16(3):455-65. doi: 10.1093/intimm/dxh045.


Rheumatoid arthritis (RA) is a polygenic autoimmune disease. The autoimmunity develops from synergistic actions of genetic and environmental factors. We generated a double-mutant mouse by crossing two murine models of RA, a gp130 mutant knock-in mouse (gp130F759/F759) and an HTLV-1 pX transgenic mouse (pX-Tg), in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously developed severe arthritis with a much earlier onset than the gp130F759/F759 mice and with a much higher incidence than did the pX-Tg mice. The symptoms of gp130F759/F759 mice, including lymphoadenopathy, splenomegaly, hyper-gamma-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHC(bright) CD11c+ population, were augmented in the double mutants. Marked reductions in incidence, severity and immunological abnormalities were seen in the triple mutant, IL-6-/-/gp130F759/F759/pX-Tg, indicating that the arthritis in the double mutant is IL-6 dependent. gp130F759/F759/pX-Tg is a unique mouse model for RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankle Joint / diagnostic imaging
  • Ankle Joint / pathology
  • Antigens, CD / genetics*
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Cytokine Receptor gp130
  • Disease Models, Animal
  • Flow Cytometry
  • Genes, pX / genetics*
  • Genes, pX / immunology
  • Human T-lymphotropic virus 1 / genetics*
  • Human T-lymphotropic virus 1 / immunology
  • Interleukin-6 / immunology
  • Lymph Nodes / cytology
  • Membrane Glycoproteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology
  • Point Mutation* / genetics
  • Point Mutation* / immunology
  • Radiography
  • Spleen / cytology
  • T-Lymphocyte Subsets / immunology
  • Tyrosine / genetics


  • Antigens, CD
  • Il6st protein, mouse
  • Interleukin-6
  • Membrane Glycoproteins
  • Cytokine Receptor gp130
  • Tyrosine